R,R-trans-2,4-dimethylazetidine | 286435-40-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: R,R-trans-2,4-dimethylazetidine
• 英文别名: trans-2,4-Dimethylazetidin；(2R,4R)-2,4-dimethylazetidine
• CAS: 286435-40-3
• 化学式: C₅H₁₁N
• 分子量: 85.149
• InChiKey: YPIDADKMTAZBST-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  R,R-trans-2,4-dimethylazetidine 、 麦角酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (2'R,4'R)-(+)-9,10-didehydro-6-methylergoline-8β-(cis-2,4-dimethylazetidide)
  参考文献：
  名称：

  Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent N,N-Diethyllysergamide (LSD)

  摘要：

  Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25. Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine gave a lysergamide with the highest LSD-like behavioral activity in the rat two lever drug discrimination model that was slightly more potent than LSD itself. This same diastereomer also had the highest affinity. and functional potency at the rat serotonin 5-HT2A receptor, the presumed target for hallucinogenic agents, and a receptor affinity profile in a panel of screens that was most similar to that of LSD itself. Both cis- and the (R,R)-trans-dimethylazetidines gave lysergamides that were less potent in all relevant assays. The finding that the S,S-dimethylazetidine gave a lysergamide with pharmacology most similar to LSD indicates that the N,N-diethyl groups of LSD optimally bind when they are oriented in a conformation distinct from that observed in the solid state by X-ray crystallography. The incorporation of isomeric dialkylazetidines into other biologically active molecules may be a useful strategy to model the active conformations of dialkylamines and dialkylamides.

  DOI：

  10.1021/jm020153s

文献信息

• Lysergamides of Isomeric 2,4-Dimethylazetidines Map the Binding Orientation of the Diethylamide Moiety in the Potent Hallucinogenic Agent <i>N</i>,<i>N</i>-Diethyllysergamide (LSD)
  作者：David E. Nichols、Stewart Frescas、Danuta Marona-Lewicka、Deborah M. Kurrasch-Orbaugh

  DOI：10.1021/jm020153s

  日期：2002.9.1

  Lysergic acid amides were prepared from (R,R)-(-)-, (S,S)-(+)-, and cis-2,4-dimethyl azetidine. The dimethylazetidine moiety is considered here to be a rigid analogue of diethylamine, and thus, the target compounds are all conformationally constrained analogues of the potent hallucinogenic agent, N,N-diethyllysergamide, LSD-25. Pharmacological evaluation showed that (S,S)-(+)-2,4-dimethylazetidine gave a lysergamide with the highest LSD-like behavioral activity in the rat two lever drug discrimination model that was slightly more potent than LSD itself. This same diastereomer also had the highest affinity. and functional potency at the rat serotonin 5-HT2A receptor, the presumed target for hallucinogenic agents, and a receptor affinity profile in a panel of screens that was most similar to that of LSD itself. Both cis- and the (R,R)-trans-dimethylazetidines gave lysergamides that were less potent in all relevant assays. The finding that the S,S-dimethylazetidine gave a lysergamide with pharmacology most similar to LSD indicates that the N,N-diethyl groups of LSD optimally bind when they are oriented in a conformation distinct from that observed in the solid state by X-ray crystallography. The incorporation of isomeric dialkylazetidines into other biologically active molecules may be a useful strategy to model the active conformations of dialkylamines and dialkylamides.